1. Technical Field
The present invention relates to a method of detecting pancreatic cancer, and more particularly to a method of detecting pancreatic cancer in which pathological haptoglobin is used as a tumor marker.
2. Background Art
Since pancreas is located deep in the body, cancer is difficult to detect if it occurs in the pancreas. Tumor markers for diagnosing pancreatic cancer include CEA (the reference value: 5.0 ng/mL) and CA 19-9 (the reference value: 37 U/mL). False-positives may, however, be included in the results from these tumor markers, and therefore reliable results may not be obtained by using the tumor markers alone. In order to confirm pancreatic cancer, expensive thorough examinations, such as computerized tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), ultrasound endoscopy (EUS), angiography, etc. are required. Among these, ERCP and EUS are invasive and may impose a burden on patients.
Recent reports state that when pancreatic cancer is developed, fucose is attached to sugar chains of haptoglobin, one of glycoproteins (Non Patent Literatures 1 and 2, and Patent Literature 1). According to Non Patent Literature 1, this pathological haptoglobin is increased as the stage of pancreatic cancer progresses, and will disappear after the tumor site of pancreatic cancer is surgically removed.
Human haptoglobin is a glycoprotein comprised of 406 amino acids, containing four N-linked glycosylation sites on its β chain (molecular weight: 40,000). Human haptoglobin is abundant in serum of healthy adults at the concentration of 0.7 to 1.7 mg/mL. The use of pathological haptoglobin as a tumor marker for pancreatic cancer including early one can be achieved by accurately detecting pathological haptoglobin out of other haptoglobin molecules.
It is conceivable that a sugar binding “lectin” can be used to obtain the information about the changes in the structure and transfer of sugar chains on the cell surface associated with canceration. Conventionally, Aleuria aurantia lectin (AAL), Lens culinaris lectin (LCA), Lotus japonicus lectin (Lotus), Ulex europaeus lectin (UEA-I), etc. are known as lectins for detecting fucose. However, detection methods that use these conventional lectins often fail to exhibit a significant difference between healthy subjects and patients with pancreatic cancer.
Citation List
Patent Literature
Patent Literature 1: Japanese unexamined patent application publication No. 2009-168470
Non Patent Literature
Non Patent Literature 1: Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation”. Okuyama N, et. al., Int J Cancer. 2006 Jun. 1; 118 (11): 2803-8
Non Patent Literature 2: Site-specific analysis of N-glycans on haptoglobin in sera of patients with pancreatic cancer: a novel approach for the development of tumor markers”. Nakano M, et. al., Int J Cancer. 2008 May 15; 122 (10): 2301-9